Cyclic hemiacetals and hemiketals

Monosaccharide structures may be depicted in open-chain forms showing their carbonyl character, or in cyclic hemiacetal or hemiketal forms. Alongside the Fischer projections of glucose, ribose, and fructose shown earlier, we included an alternative 

Both six-membered pyranose and five-membered furanose structures are encountered, a particular ring size usually being characteristic for any one sugar. Thus, although glucose has the potential to form both six-membered and five-membered rings, an aqueous solution consists almost completely of the six-membered hemiacetal form five-membered rings 

The pentose ribose is also able to form six-membered pyranose and five-membered furanose rings. In solution, ribose exists mainly (76%) in the pyranose form interestingly, however, when we 

Fructose is a ketose and, therefore, forms hemike-tal ring structures. Like ribose, it is usually found in combination as a five-membered furanose ring. 

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The position of equilibrium, i.e. whether the carbonyl compound or the addition product is favoured, depends on the nature of the reagents. The equilibrium constant is often less than 1, so that the product is not favoured, and many simple hemiacetals and hemiketals are not sufficiently stable to be isolated. However, stable cyclic hemiacetals and hemiketals... 

The cyclic hemiacetal and hemiketal forms of monosaccharides are capable of reacting with an alcohol to form acetals and ketals (see Section 7.2). The acetal or ketal product is termed a glycoside, and the non-carbohydrate portion is referred to as an aglycone. In the nomenclature of glycosides we replace the suffix -ose in the sugar with -oside. Simple glycosides may be synthesized by treating an alcoholic solution of the monosaccharide with an acidic catalyst, but the reaction mixture usually then contains a mixture of products. This is an accepted problem with many carbohydrate reactions it is often difficult to carry out selective transformations because of their multifunctional nature. 

The actual structure of monosaccharides such as o-glucose is not what has been shown up to this point. We previously learned that aldehydes and ketones react reversibly with alcohols to form hemiacetals and hemiketals, respectively. (Refer back to Sec. 14.7 to review this reaction.) This reaction takes place intramolecularly with monosacchardes since both OH and C = O are present in the same molecule. The structures of aldoses and ketoses are cyclic hemiacetals and hemiketals, respectively. 

Ans. The cyclic hemiacetal and hemiketal structures have no carbonyl function but are in equilibrium with the open-chain carbonyl structure. As the small amount of the open-chain carbonyl structure reacts, some of the a- and /3-anomers undergo ring-opening to replenish the equilibrium concentration of the open-chain structure. The newly formed open-chain structure undergoes reaction. More a- and -anomers open up. There is a continuous shifting of a- and /3-anomers to the open-chain carbonyl structure until all of the monosaccharide initially present has reacted. 

Cyclic hemiacetals and hemiketals are much more stable than the open-chain compounds discussed earlier. In Chapter 7, we ll see that sugars such as glucose and fructose exist predominantly in the form of cyclic hemiacetals and hemiketals. 

Although carbohydrate cyclic hemiacetals and hemiketals are in equilibrium with open-chain forms of the monosaccharides, the glycosides (acetals and ketals) are much more stable and do not exhibit open-chain forms. Therefore, glycosides of monosaccharides are not reducing sugars. 

Cyclic hemiacetals and hemiketals also react with alcohols to produce cyclic acetals and cyclic ketals. We will see this reaction again when we consider carbohydrates in Chapter 24. 

The cyclic hemiacetal or hemiketal forms of aldo- and ketohexoses and pentoses are the predominant forms of these sugars, rather than the open-chain structures we have discussed to this point. Cyclic hemiacetals and hemiketals of carbohydrates that contain five-membered rings are called furanoses. Cyclic hemiacetals and hemiketals that contain six-membered rings are called pyranoses. These names are based the cyclic rings of furan and pyran. 

However, it is important to keep in mind that the carbonyl groups of sugars usually are combined with one of the hydroxyl groups in the same molecule to form a cyclic hemiacetal or hemiketal. These structures once were written as follows, and considerable stretch of the imagination is needed to recognize that they actually represent oxacycloalkane ring systems ... 

When a monosaccharide forms a cyclic hemiacetal (or hemiketal), the carbonyl carbon becomes a stereocenter. Thus, cyclization leads to formation of two possible stereoisomers. These isomers are called anomers, and the former carbonyl carbon is called the anomeric carbon. The isomer with the anomeric OH (shown in blue) pointed down is the alpha anomer. The isomer with the anomeric OH (shown in blue) pointed up is the beta anomer. (Figure 12.14)... 

Monosaccharides, polyhydroxy aldehydes or ketones, are either aldoses or ketoses. Sugars that contain four or more carbons primarily have cyclic forms. Cyclic aldoses or ketoses are hemiacetals and hemiketals, respectively. 

Hemiacetals and hemiketals react with alcohols to form acetals and ketals, respectively. When the cyclic hemiacetal or hemiketal form of a monosaccharide reacts with an alcohol, the new linkage is called a glycosidic linkage, and the compound is called a glycoside. 

Hemiacetals and hemiketals are readily formed in carbohydrates. Monosaccharides contain several hydroxyl groups and one carbonyl group. The linear form of a monosaccharide quickly undergoes an intramolecular reaction in solution to give a cyclic hemiacetal or hemiketal. 

The cyclic hemiacetal (or hemiketal) can react with an alcohol to form an acetal (or ketal), called a glycoside. If the name pyranose or furanose is used, the acetal is called a pyranoside or a furanoside. The bond between the anomeric carbon and the alkoxy oxygen is called a glycosidic bond. The preference for the axial position by certain substituents bonded to the anomeric carbon is called the anomeric effect. If a sugar has an aldehyde, ketone, hemiacetal, or hemiketal group, it is a reducing sugar. 

Toward the end of the nineteenth century, it was realized that the free sugars exist as cyclic hemiacetals or hemiketals. Individual sugars react with methanol under acid catalysis to give stable products termed methyl glycosides, which are mixed full acetals. These have a new asymmetric center at the original carbonyl atom and were thus isolated as pairs of isomers that were designated as the ot and p forms, later termed anomers. In the d series, the a anomer was defined as the one having the more-positive specific rotation, and in the l series, the a anomer... 

Some molecules contain both an —OH and a C=0 group on different carbon atoms. In such cases, an intramolecular (within the molecule) reaction can occur, and a cyclic hemiacetal or hemiketal can be formed ... 

In Section 4.3, we learned that hemiacetals and hemiketals can react with alcohols in acid solutions to yield acetals and ketals, respectively. Thus, cyclic monosaccharides (hemiacetals and hemiketals) readily react with alcohols in the presence of acid to form acetals and ketals. The general name for these carbohydrate products is glycosides. The reaction of a-D-glucose with methanol is shown in Reaction 7.6. 

Monosaccharides are sweet-tasting solids that are very soluble in water. Noncarbohydrate low-calorie sweeteners such as aspartame have been developed as sugar substitutes. Pentoses and hexoses form cyclic hemiacetals or hemiketals whose structures can be represented by Haworth structures. Two isomers referred to as anomers (the a and p forms) are produced in the cyclization reaction. All monosaccharides are oxidized by Benedict s reagent and are called reducing sugars. Monosaccharides can react with alcohols to produce acetals or ketals that are called glycosides. 

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